Usefulness of laparoscopic surgery for colorectal perforation: a single-center retrospective cohort study.

PURPOSE: This study aimed to determine the safety and efficacy of laparoscopic surgery in patients with colorectal perforation owing to a significant lack of evidence in this field. METHODS: This retrospective cohort study analyzed the data of 70 patients who underwent emergency surgery for colorectal perforations between January 2017 and December 2023. The surgical outcomes of the patients who underwent open and laparoscopic surgeries were statistically compared. The primary endpoints were postoperative mortality and complications. The secondary endpoints included blood loss, surgical time, length of hospital stay, and 1-year overall survival. RESULTS: Overall, 28 patients underwent open surgery and 42 underwent laparoscopic surgery. No significant difference was noted in the postoperative mortality or overall rate of severe complications between the two groups. The incidence of superficial and deep incisional surgical site infection was lower in the laparoscopic surgery group (35.7% vs. 0.0%, p < 0.001), while the surgical time was significantly longer in the laparoscopic group (175.6 ± 92.2 min vs. 290.0 ± 102.3 min, p < 0.001). No significant differences were found in blood loss, length of hospital stay, or 1-year overall survival. CONCLUSIONS: Laparoscopic surgery for colorectal perforation markedly reduced superficial and deep incisional surgical site infection, with no substantial difference in mortality or severe complications.

Xanthogranulomatous appendicitis presenting asymptomatically 3 years after surgery for hilar cholangiocarcinoma: A case report.

INTRODUCTION: Xanthogranulomatous appendicitis (XGA) is a rare condition involving chronic inflammation of the appendix that is often difficult to distinguish from malignancy using imaging because of the formation of a heterogeneous mass with indistinct borders. Herein, we present a case of XGA with unusual clinical manifestations. PRESENTATION OF CASE: A 78-year-old female patient underwent radical resection of hilar cholangiocarcinoma with extended right hepatic lobectomy and biliary reconstruction. Three years postoperatively, she presented with an irregular mass in the right lateral pelvis, which was observed on computed tomography. The patient had not experienced recent clinical symptoms and did not present with abdominal tenderness. Routine blood tests did not indicate an increased inflammatory response; however, carcinoembryonic antigen levels continued to increase. Although disseminated recurrence of hilar cholangiocarcinoma and appendiceal carcinoma were suspected, XGA was diagnosed via laparoscopic appendectomy. DISCUSSION: XGA generally presents with symptoms of acute or chronic appendicitis, and is diagnosed incidentally during surgery. Hilar cholangiocarcinoma has a high recurrence rate, even after radical resection, and disseminated recurrence usually requires chemotherapy. In the present case, XGA was not suspected preoperatively because of the lack of physical symptoms and increased levels of tumor markers during follow-up for hilar cholangiocarcinoma. There have been no reports of XGA with such a confusing clinical course, thus confirming the difficulty in preoperatively diagnosing XGA. CONCLUSION: The preoperative diagnosis of XGA is difficult to differentiate from malignancy because of its clinical and imaging findings. We diagnosed the patient with XGA using laparoscopic surgery.

Minimally Invasive Conversion Surgery for Unresectable Gastric Cancer with Splenic Metastasis and Splenic Vein Tumor Thrombus: A Case Report.

While the importance of conversion surgery has increased with the development of systemic chemotherapy for gastric cancer (GC), reports of conversion surgery for patients with GC with distant metastasis and tumor thrombus are extremely scarce, and a definitive surgical strategy has yet to be established. Herein, we report a 67-year-old man with left abdominal pain referred to our hospital following a diagnosis of unresectable GC. Esophagogastroduodenoscopy and contrast-enhanced abdominal computed tomography (CT) revealed advanced GC with splenic metastasis. A splenic vein tumor thrombus (SVTT) and a continuous thrombus to the main trunk of the portal vein were detected. The patient was treated with anticoagulation therapy and systemic chemotherapy comprising S-1 and oxaliplatin. One year following chemotherapy initiation, a CT scan revealed progressive disease (PD); therefore, the chemotherapy regimen was switched to ramucirumab with paclitaxel. After 10 courses of chemotherapy resulting in primary tumor and SVTT shrinkage, the patient underwent laparoscopic total gastrectomy (LTG) and distal pancreaticosplenectomy (DPS). He was discharged without complications and remained alive 6 months postoperatively without recurrence. In summary, the wait-and-see approach was effective in a patient with GC with splenic metastasis and SVTT, ultimately leading to an R0 resection performed via LTG and DPS.

Small bowel volvulus associated with percutaneous endoscopic gastrojejunostomy tube: A case report.

INTRODUCTION: Percutaneous endoscopic gastrojejunostomy (PEG-J) is a convenient and safe enteral feeding tool for patients with oropharyngeal dysfunction accompanied by gastroesophageal reflux. However, serious complications have not been fully characterized. PRESENTATION OF CASE: A 22-year-old man with cerebral palsy was referred to our department with complaints of vomiting and massive bloody stools for 10 h. On imaging examination, strangulated bowel obstruction due to the PEG-J tube was suspected because the tube was located on the right side of the body, and the small intestine was diffusely dilated with a reduced wall contrast effect. Urgent laparoscopy revealed a small bowel volvulus (SBV) twisted 180° clockwise around the superior mesenteric artery, which was repaired manually without intestinal resection. The patient was treated in the intensive care unit postoperatively but required partial ileal resection and colostomy owing to the difficulty in managing watery diarrhea and intestinal infection. The patient was discharged after stoma closure 121 days after initial surgery. DISCUSSION: Although SBV rotated at the site of PEG insertion has been reported as a rare complication, there are no reports of rotation of the PEG-J tube itself associated with SBV. In the present case, abnormal positioning of the PEG-J tube on imaging was helpful for diagnosis. CONCLUSION: SBV should be recognized as a potential complication of PEG-J, since delayed diagnosis can lead to irreversible ischemia of the extensive small intestine.

Pneumothorax during lenvatinib treatment for hepatocellular carcinoma with lung metastasis.

Lenvatinib is an inhibitor of tyrosine kinases, such as vascular endothelial growth factor receptor and fibroblast growth factor receptor, and was first approved for use in thyroid cancer in 2015 in Japan. Additional approval was given in March 2018 for its use as a first-line treatment for advanced or unresectable hepatocellular carcinoma. Herein, we report a case of pneumothorax during lenvatinib treatment for multiple lung metastases of hepatocellular carcinoma in a 71-year-old man. Although the development of pneumothorax during treatment with anticancer agents for lung metastases is well-known, this is the first report of pneumothorax induced by lenvatinib during treatment for lung metastases of hepatocellular carcinoma.

Lymph node retrieval after colorectal cancer surgery: a comparative study of the efficacy between the conventional manual method and a new fat dissolution method.

PURPOSE: This study compared the efficacy of two different methods for lymph node (LN) searching after colorectal cancer surgery: the fat dissolution and the conventional manual method. METHODS: For the fat dissolution method, we used a commercially available solution of collagenase and lipase (FD group). The primary endpoint was the number of identified LNs in the FD group compared to an historical control (control group) after adjusting by propensity score matching. RESULTS: Using 37 matched patients from each group, we identified 20.6 ± 7.2 LNs using the fat dissolution method compared to 13.5 ± 5.9 using the conventional method (t test, P < 0.01). Three patients in the FD group received an inappropriate LN examination in terms of number, while the number of the retrieved LNs was < 12 in 12 patients in the control group. The mean diameter of LNs without metastasis was 3.2 ± 1.9 mm in the FD group, and 40% of metastasis cases were found in LNs < 5 mm in diameter. A pathological examination confirmed that using the fat resolution method did not change the morphological or immunochemical staining findings. CONCLUSION: We demonstrated that fat dissolution had a positive impact on the number of retrieved LNs after colorectal cancer surgery without disturbing the microscopic observation.

Visualization of the Stomach's Arterial Networks During Esophageal Surgery Using the HyperEye Medical System.

AIM: The present study investigated the visualization of the arterial networks in the stomach (ANS) during gastric tube (GT) creation using indocyanine green fluorescence and the HyperEye Medical System (HEMS), and the feasibility of the HEMS-line-marking method (LMM). PATIENTS AND METHODS: We reviewed 51 consecutive patients who had undergone esophageal surgery with GT reconstruction. Patients for whom the HEMS was deployed after GT creation to confirm the anastomosed area's blood supply formed the control group (n=28). Patients for whom the HEMS was deployed before GT creation to confirm and mark the ANS border comprised the HEMS-LMM group (n=23). RESULTS: The HEMS-LMM visualized the ANS border, and the leakage rate decreased from 17.9% to 4.4% (p=0.204). CONCLUSION: The HEMS-LMM is safe and feasible for visualizing the blood supply border of the right gastroepiploic artery and the ANS before GT creation during esophageal surgery, and it might reduce leakage in esophageal surgery.

Rarity of late anastomotic leakage after low anterior resection of the rectum.

BACKGROUND: Late anastomotic leakage is reported to account for half of all anastomotic leakages after low anterior resection of the rectum. An important clinical question is whether late and early anastomotic leakages are different entities. METHODS: We retrospectively reviewed the medical records of patients who experienced anastomotic leakage after low anterior resection in two Japanese hospitals. The clinical characteristics were extracted and analyzed. RESULTS: During the study period, 179 patients underwent low anterior resection. A pelvic drainage tube was routinely utilized in all cases and was generally removed 4 to 6 days after the operation. Twenty-six patients had anastomotic leakage; the diagnosis was based on fecal contamination of the drainage in 24 cases. The median interval between operation and detection of anastomotic leakage was 3.5 days. Anastomotic leakage was diagnosed within 7 days of the operation in 25 cases and on postoperative day 20 (after hospital discharge) in one case. There was no instance of anastomotic leakage diagnosed more than 30 days after the operation. There was no relationship between clinical variables and days of leakage diagnosis. CONCLUSION: The rarity of late anastomotic leakage in our study, compared with previous studies, may relate to the relatively extended period of pelvic drainage tube usage in our institutes, which likely shortens the interval before leakage diagnosis. Our results suggest that late anastomotic leakage is a delayed symptom of subtle early anastomotic leakage rather than a separate entity.

Staged surgery after colonic decompression may be safer for the treatment of obstructive left-sided colorectal cancer in a non-specialized hospital.

BACKGROUND/AIMS: The management for the obstructive left sided colorectal cancer is still controversial. METHODOLOGY: A retrospective study was performed on 249 consecutive patients who underwent surgical intervention for left sided colorectal cancer in our hospital. Among 36 patients who had colonic obstruction, 25 patients received tumor resection while the rest of the patients received palliative stoma creation. Clinical characteristics and outcome following tumor resection was compared between patients with and without colonic obstruction. RESULTS: Prior to tumor resection, all patients received colonic decompression. Flowingly, 20 patients received staged surgeries and five patients underwent one stage surgery, with three of the latter requiring reoperation due to anastomotic leakage. The five-year overall survival rate for patients following tumor resection was 75.5 % and 69.1 % for those with and without colonic obstruction respectively. Log-rank test showed no significant difference in overall survival between the two groups (p = 0.91). CONCLUSIONS: Onestage surgery for patients with obstructive colorectal cancer in our hospital was associated with frequent anastomotic leakage. Colonic obstruction itself may not be a poor prognostic factor when decompression preceded surgical resection.

Efficacy of laparoscopic gastric mobilization for esophagectomy: comparison with open thoraco-abdominal approach.

BACKGROUND: Less invasive esophagectomy using laparoscopic or thoracoscopic surgery has been reported to have the advantages in short-term recovery over the conventional open thoraco-abdominal approach. However, few reports directly compare laparoscopic gastric mobilization (LGM) and thoracotomy with laparotomy and thoracotomy. The aim of this study was to prove the clinical efficacy of LGM compared with open thoraco-abdominal esophagectomy (OE) in treating thoracic esophageal cancer. PATIENTS AND METHODS: We retrospectively reviewed 92 consecutive patients who underwent esophagectomy by OE (n=47) or LGM (n=45) between 1999 and 2009 at Kochi Medical School (Kochi, Japan) to analyze the surgical outcomes. RESULTS: Patients who underwent LGM had significantly lower operative blood loss (430 versus 1060 mL; P<.001), lower rate of postoperative infections (POIs) (33.3 versus 55.3%; P=.034), shorter length of intensive care unit stay (1 versus 3 days; P<.001), and hospital stay (35 versus 46 days; P=.003). CONCLUSIONS: LGM has clinical benefits compared with OE in reduced POIs and faster recovery for patients with esophageal cancer.

Quantitative distribution of brush cells in the rat gastrointestinal tract: brush cell population coincides with NaHCO3 secretion.

The function of brush cells is obscure, but recent cytochemical studies indicate that rat bile duct brush cells secrete NaHCO(3). The aim of this study was to determine the quantitative distribution of brush cells at 16 sites of the rat gastrointestinal tract and to investigate the role of NaHCO(3) secretion at these sites. Specimens of 16 sites of the gastrointestinal tracts of three female Long-Evans rats were fixed in a periodate-lysine-paraformaldehyde solution. Frozen sections were stained with the anti-cytokeratin 18 antibody, a selective marker for brush cells. The numbers of brush cells were counted from photographs. The percentages of brush cells in the epithelium at the 16 sites were gastric groove, 32.3%; corpus adjacent to the gastric groove, 2.5%; corpus, 0.4%; antrum, 0.4%; duodenum adjacent to the pyloric ring, 2.3%; proximal duodenum, 0%; duodenum facing the bile duct orifice, 0%; distal duodenum, 0.2%; proximal jejunum, 0.1%; transitional site between the jejunum and the ileum, 0.1%; distal ileum, Peyer's patch dome, 1.5%; and the villi, 0.4%; caecum, 2.1%; proximal colon, 0.2%; middle colon, 0.1%; distal colon, 0.1%; and rectum, 0.1%. We concluded that the population of brush cells is high in the gastric groove, the duodenum adjacent to the pyloric ring, and the caecum, where NaHCO(3) is postulated to neutralize gastric HCL or organic acids produced by enteric bacteria. The brush cell population is low in the duodenum and jejunum, which receive bile and pancreatic juice.

Vascular endothelial growth factors and their receptors in the novel human cell line, HN-Eso-1, established from esophageal spindle cell carcinoma.

Human carcinosarcomas of esophagus are uncommon malignant neoplasms that are composed both carcinomatous and sarcomatous components. We established a novel cell line, HN-Eso-1, from the metastatic esophageal spindle cell carcinoma (so-called carcinosarcoma). In this study, we estimated the vascular endothelial growth factors (VEGFs) and VEGF receptors (VEGFRs). Reverse transcription polymerase chain reaction (RT-PCR) studies revealed that VEGF-A, -C, -D and VEGFR-1, -2 were upregulated. Cisplatin reduced the cell viability of HN-Eso-1 cells and VEGF attenuated its effect. These results suggest that expression of VEGF-A, VEGF-C, VEGF-D, VEGFR-1, and VEGFR-2 are involved in the cell's autocrine system and that VEGF protected these cells from the anti-tumor agent.

Better postoperative oxygenation in thoracoscopic esophagectomy in prone positioning.

Intrathoracic procedures can be performed with thoracoscopy in esophagectomy because the laparoscopic technique has recently been developed. During intrathoracic procedures, prone positioning of the patient allows gravity to facilitate optimal exposure of the esophagus, thereby affording a superb surgical view. In the current study, we compared the influence of prone positioning with lateral decubitus positioning on oxygenation in esophagectomy. We enrolled 18 patients and divided them into two groups: patients who underwent esophagectomy via thoracoscopy in the prone position (group P) and patients who underwent thoracotomy in the lateral decubitus position (control group, group L). Arterial blood gas analyses were performed before the operation was started (T1), 20 min after the initiation of one-lung ventilation (OLV) (T2), and two other points. The P/F ratio at T2 in group P was higher. Further, percent (%) change of the P/F ratios from T1 and thereafter in group P was higher at all points. We thought the reason why the prone position had contributed to maintenance oxygenation was as follows. First, the functional residual capacity and ventilation/perfusion matching in the prone position are satisfactory. Second, a bronchial blocker might contribute to reduction of atelectasis. Third, minimally invasive esophagectomy might reduce respiratory complications and blood loss because this procedure reduces edema and inflammation in the lung. In conclusion, the oxygenation provided by prone positioning is better than that provided by the lateral decubitus position during OLV in esophagectomy.

[A case of small cell undifferentiated carcinoma of the esophagus successfully treated by chemoradiotherapy].

Small cell carcinoma of the esophagus is rare, with a poor prognosis, and there is currently no standard therapy. Here we report a case of small cell carcinoma of the esophagus with right supraclavicular lymph node metastasis which was successfully treated by chemoradiotherapy. A 55-year-old man was admitted to our hospital with a right-sided neck tumor. The neck tumor was diagnosed as a small cell carcinoma by aspiration cytology. Endoscopy revealed an irregular tumor in the middle thoracic esophagus, 31 cm from the upper incisor teeth, but malignant cells were not detected from an esophageal biopsy. Right supraclavicular lymph node metastasis was detected by computed tomography and positron emission tomography computed tomography, and aspiration cytology revealed small cell undifferentiated carcinoma cells. The patient was diagnosed with a small cell carcinoma of the esophagus with supraclavicular lymph node metastasis, stage III: T2N3M0. Concurrent chemoradiotherapy using 5-fluorouracil and cisplatin was started. Lymph node reduction occurred from day 3, and endoscopy two months after chemoradiotherapy showed only a scar. We diagnosed the patient in complete remission, and he continues to do well with a recurrence-free status of 14 months after initial chemoradiotherapy.

Total laparoscopic gastric mobilization for esophagectomy.

BACKGROUND AND AIMS: The operative mortality and morbidity associated with esophageal surgery has been decreasing with advances in surgical techniques and equipment, however, postoperative complication remains a major cause of a potentially fatal outcome. We herein describe a new technique for esophagectomy by total laparoscopic gastric mobilization technique as a minimally invasive surgery. PATIENTS AND METHODS: Between April 2003 and August 2007, 36 patients who were suffering from esophageal cancer were surgically resected at Kochi Medical School. Operation-related parameters, mortality, postoperative complication, intubation time, and length of surgical intensive care unit in patients with total laparoscopic gastric mobilization for esophagectomy (the TLGM group, n = 16) were evaluated, compared to patients with ordinary thoraco-abdominal esophagectomy (the OPEN group, n = 20). RESULTS: There was no mortality in the TLGM group and one hospital death in the OPEN group. Operation time of the OPEN group (506 +/- 64 min) was significant shorter than that of the TLGM group (558 +/- 67 min). The estimated intraoperative blood loss volume in patients of the TLGM group (496 +/- 259 mL) was much smaller than those of the OPEN group (1,067 +/- 566 mL). The intubation time and the intensive care unit stay in the TLGM group were much shorter than that in the OPEN group. CONCLUSIONS: Esophagectomy with regional lymphadenectomy combined with total laparoscopic gastric mobilization is a safe and beneficial opportunity for patients who underwent surgical procedure for esophageal cancer.

Immunohistochemical and electron microscopic characterization of brush cells of the rat cecum.

Brush cells (BCs) are relatively rare cells that are sparsely distributed throughout the mammalian digestive and respiratory systems. BCs have been identified in the rodent large intestine, but these cells have not been characterized by immunocytochemistry or electron microscopy. We previously demonstrated that rat bile duct BCs had strong immunoreactivity for six proteins that function in HCO(3)(-) secretion and thus assumed that BCs secrete NaHCO(3). It is well known that the gastrointestinal (GI) tract secretes NaHCO(3), but it is not known whether BCs of the GI tract also express proteins related to HCO(3)(-) secretion. Thus, in the present study, using double immunostaining for cytokeratin 18, a specific marker for BCs, we investigated protein expression in BCs from the rodent GI tract. We show that BCs from the GI tract express six proteins related to HCO(3)(-) secretion: cystic fibrosis transmembrane conductance regulator (CFTR), Cl(-)/HCO(3)(-) exchanger, Na(+)/HCO(3)(-) cotransporter, carbonic anhydrase II, Na(+)/H(+) exchanger (NHE) 1, and NHE3. These results suggest that BCs from the GI tract secrete NaHCO(3). In addition, we examined BCs from the rat cecum using electron microscopy (EM). Transmission EM (TEM) showed that BCs have long microvilli, a well-developed tubulovesicular system, and an abundant cytoskeleton. Scanning EM revealed that BCs were scattered on the luminal surface of the cecum and had numerous long microvilli.

Recurrence of gastric cancer in the jejunal pouch after completion gastrectomy.

We herein present a case of recurrence of gastric cancer in the jejunal pouch after total gastrectomy in a 74-year-old man. He had a history of two operations for gastric cancer. The second operation was a completion gastrectomy with jejunal pouch reconstruction and regional lymphadenectomy, for gastric cancer in the cardia of the remnant stomach, performed 2 years and 9 months before the present admission. A follow-up endoscopy showed three elevated tumors along the suture lines in the jejunal pouch in the upper digestive tract. Resection of the jejunal pouch was performed. Gross pathological examination revealed elevated lesions along the staple suture lines in the jejunal pouch. Histopathologically, moderately differentiated tubular adenocarcinoma involving the muscular layer, without lymphatic metastases, was recognized. Recurrence of gastric cancer in the jejunal pouch after resection is rare. We suggest that implantation of exfoliated cancer cells gave rise to the recurrence of tumors on the suture line in this patient. We also review two cases of gastric cancer in the jejunal pouch after resection previously described in the literature.

Clinicopathological analysis of idiopathic perforation of the gallbladder.

Idiopathic perforation of the gallbladder (IPGB) is a rare event, and the underlying mechanisms are unknown. We investigated the clinicopathological characteristics of this disorder. We reported a case of IPGB, and reviewed 30 other cases reported up to the end of 2005 in a Medline and Japan Centra Revuo Medicina search of the medical literature. We analyzed the clinical findings, laboratory data, and histopathological features. The mean age of the patients was 70.2 +/- 12.8 years, and there were 19 men and 12 women. Underlying diseases such as hypertension, cerebral infarction or hemorrhage, renal failure, respiratory failure, and malignancy were reported in 35.5% of the patients. Perforation was found more often in the fundus (53.3%) than in the body (43.3%) or neck (3.3%) of the gallbladder. Thrombus was found in the intramural vessels of the gallbladder wall in 13 patients (50%), whereas 13 (50%) were free of thrombus. Serum amylase was significantly higher in the intramural vessels in the thrombus-negative group than in the thrombus-positive group. The overall operative mortality was 3.3%. Univariate and multivariate analyses indicated that a delay of more than 24 h from the manifestation of symptoms to operation and a perforation size greater than 2 cm required significantly longer hospitalization. Thrombosis in the intramural vessels seems to be related to the events leading to IPGB; however, it is difficult to consider it the only cause. Early operation and the size of the perforation are important determinants of the outcome of treatment for IPGB.

Anti-reflux pouch-esophagostomy after total gastrectomy.

The most prominent and severe complication after a total gastrectomy is severe reflux esophagitis. We have developed a procedure involving jejunal pouch-esophagostomy to avoid such postoperative reflux. The novel procedure reported here initially involves folding a jejunal segment of approximately 35 cm in length. A side-to-side jejuno-jejunostomy at the anti-mesenteric side was then affected using a 100-mm linear stapler. This resulted in a jejunal pouch, 10 cm in length, and a 7-cm apical section of unstapled jejunal loop. Finally, an esophago-jejuno end-to-side anastomosis (pouch-esophagostomy) was formed at the right anterior wall of the apical bridge using a circular stapler. We have therefore introduced a "partial posterior fundoplication"-like wrapping technique to the standard gastrectomy using the apical bridge of the jejunal pouch. Only a little postoperative reflux was revealed by barium meal testing - even in the Trendelenburg's position - in patients treated with the described anti-reflux anastomosis procedure. Jejunal pouch reconstruction with partial posterior wrapping is a useful procedural addition for minimizing reflux esophagitis following a total gastrectomy.

Anti-reflux pouch-esophagostomy after proximal gastrectomy with jejunal pouch interposition reconstruction.

Reflux esophagitis is a serious postoperative complication for patients undergoing gastrectomy. We designed a new jejunal pouch-esophagostomy to prevent reflux after proximal gastrectomy. After proximal gastrectomy, ajejunal segment about 17 cm long was folded. Side-to-side jejuno-jejunostomy was made using a linear stapler with 100-mm staples along the length at the anti-mesenteric side. A 10-cm-longjejunal pouch with a 7-cm-long apical bridge was made. Esophago-jejuno end-to-side anastomosis (pouch-esophagostomy) was made with circular stapler at the right anterior wall the apical bridge. We add "partial posterior fundoplication" like wrapping using the apical bridge of the jejunal pouch. Patients with this new anti-reflux anastomosis showed no reflux on barium meal study even in the right anterior oblique deep Trendelenburg's position. Jejunal pouch reconstruction with partial posterior wrapping provides a satisfactory result with regard to preventing reflux esophagitis.