To determine the efficacy of the operative procedures for reflux esophagitis, the 30 patients including 8 patients with esophageal stricture (shortening) were retrospectively reviewed. Twenty-two of the 30 patients with noncomplicating Grade O-III esophagitis underwent the modified Hill technique plus 270-degree fundoplication. The AFP grade was determined for 12 of the 22 patients before and after the operation. All 12 patients improved in A grading, 11 patients (92%) improved in F grading, and 10 patients (83%) improved in P grading after the operation. Intraoperative esophageal manometry showed a significant elevation of lower esophageal sphincter pressure (LESP) after the repair (18.4-38.2 mmHg). Among the 8 patients with esophageal stricture, 4 underwent the Collis-Nissen operation, 3 with dilatable stricture underwent Belsey Mark IV repair, and one with an undilatable stricture underwent resection of the lower esophagus and cardia. Reflux symptoms have recurred in 2 patients treated by inadequate fundoplication of the Collis-Nissen operation. Three patients treated with Belsey-Mark IV repair have been relieved of reflux with adequate levels of LESP after the operation (11.0 mmHg, 18.7 mmHg and 31.3 mmHg). In conclusion, a modified Hill technique plus 270-degree fundoplication is a suitable procedure for noncomplicating reflux esophagitis, and Belsey Mark IV repair is a useful operation for complicating reflux esophagitis with stricture. Preopertive dilatation and esophageal manometry are essential to indicate the need for an operative procedure for reflux esophagitis with stricture.

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The expression of PCNA, laminin (LN), p53, nm23 and c-erbB-2 detected by immunohistochemical staining was investigated by using paraffin-embedded specimens obtained from 25 (m, 2; sm, 23) early gastric cancer patients with lymph node metastasis (n+) for 16 years starting in 1977 and compared with those of 56 (m, 44; sm, 12) early gastric cancer patients without lymph node metastasis n (-) for 3 years starting in 1982. The PCNA labeling index of n (+) was 53.0±20.0% on average, which was significantly higher than that of n (-), 35.0±21.4%. The rates of positive nm23 and c-erbB-2 of n (+) were significantly higher than those of n (-), while, there was no significant difference in the rates of positive laminin and p53 between n (+) and n (-). As a conclusion, it is suggested that the investigation of PCNA, nm23 and c-erbB-2 in early gastric cancer might be important in predicting tumor behavior and screening of the patients as a higher risk factor in lymph node metastases.

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We investigated clinicopathologically gastric cancer invasion into the proper muscle layer (mp), and the relation of flowcytometric DNA content to prognosis was determined. There was no correlation between DNA ploidy and clinicopathological variables, such as age, gender, location, macroscopic type, histology, nodal status, peritoneal metastasis, liver metastasis and staging. Fifty-nine percent of the cancers were dipolid and 41% were aneuploid, and the 5-year survival rates were 89% and 50%, respectively. Nodal status, DNA ploidy and liver metastasis were the significant prognostic variables in a univariate analysis, and the first two were also significant in a multivariate analysis. The DNA ploidy pattern in mp gastric cancer is considered to be an independent prognostic factor.

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Histologic features in 176 cases of submucosal invasive gastric carcinoma were investigated. Thirty (28.5%) of 105 well-differentiated intramucosal adenocarcinomas became poorly differentiated in the submucosal layer, whereas each of the 71 poorly differentiated intramucosal adenocarcinoma had the same histological features as the infiltrate. The mode of invasion of the carcinoma to the submucosal layer and its intramucosal histologic features were correlated. Eighty-nine percent of poorly differentiated intramucosal adenocarcinomas had invaded the submucosal layer in a nonsolid manner, whereas 65% of well-differentiated intramucosal adenocarcinomas had spread in a solid manner. Five of 18 patients (28%) in whom the histologic diagnosis had changed from well-differentiated adenocarcinoma to poorly differentiated carcinoma with solid spread from the intramucosal to the submucosal layer died of the disease and tended to have intestinal-type mucin. Patients with these histologic features are at a high risk for recurrence and should receive adjuvant therapy, even if they have undergone curative resection for early gastric carcinomas.

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Forty-eight gastric cancer patients with peritoneal recurrence after thecurativeoperations were analyzed retrospectively. The distribution of n-staging in the general rules forgastric cancer established by the Japanese Research Society was 22 cases with n₁ and 12 cases with n₂.Among these, 23 gastric cancers had infiltrated the connective tissue around lymph nodes. The ratios ofmale and tumors located in A region were significantly increased in cases with cancer cells infiltratingaround lymph nodes as compared to cases without such infiltrative cancer cells (p<0.05). Theincidence of infiltration to connective tissue around lymph nodes was 31.8% in n₀, 57.1% in n₁, 66.7% in n₂.The microscopic mode of cancer cell infiltration was classified into extra-nodal invasion in 12 casesand very small disseminated metastasis in 11 cases. The extranodal invasion mode was frequently recognizedin cases with lymph node involvement. These lesions were often found at perigastric lymph nodes in thegreater or lesser omentum and were presumed to carry a diagnosis of P₁ according to the general rules forgastric cancer established by the Japanese Research Society. It is difficult to diagnose these P₁ lesionsmacroscopically and intraoperatively. Therefore, intraoperative pathological diagnosis of cancercells infiltrating around lymph nodes is recommended for propylactic treatment against peritonealrecurrence.

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The benefits of ultrasound in the diagnosis of strangulation obstruction were investigated in 78 patients with adhesive intestinal obstruction (simple: strangulation=70: 8). Although small bowel dilatation exceeding 3 cm in diameter, ascites, and a dilated bowel loop containing sediments of debris are three features specific to strangulation obstruction, ultrasonographic properties of ascites and intestinal wall changes are not. We classified patients with adhesive intestinal obstruction into 3 grades based on three ultrasonographic aspects; grade 1 included zero to one of these features (simple: strangulation=48: 0), grade 2 included with two features (simple: strangulation=21: 1), and those with grade 3 included all three (simple: strangulation=1: 7). Therapeutic strategies were determined according to each grade; patients with grade 1 should be treated for simple intestinal obstruction, those with grade 2 require close observation because of the possibility of strangulation, those with grade 3 must be operated upon for strangulation. This classification using ultrasound is very useful for the treatment of patients with intestinal obstruction.

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Seventy five cases had undergone hepatic resection for liver metastases from colorectal cancer from 1979 to 1994. Computed tomography during hepatic angiography (angio CT) was tried in 27 cases. At first, we compared detection ratios of angio CT for liver metastase to those of ultrasonography, conventinal CT, and operative ultrasonography on these 27 cases. Next, the prognosis of seventy five cases was examined. They were divided into three groups: the HX group 29 cases with only hepatic resection: the HX+AP group of 19 cases with intermittent hepatic arterial infusion chemotherapy after hepatic resection: the angio CT group of 27 cases selected for hepatic resection by angio CT, followed by the same infusion chemotherapy as that given to the HX+AP group. Fifty metastases were diagnosed histopathologically in twenty seven cases that underwent hepatic resection after angio CT. Detection ratios for small metastases 1.0 cm or smaller in diameter were 8.3% with ultrasonography, 25% with CT, 75% with angio CT, and 50% with operative ultrasonography. Detection ratios of angio CT were superior to those of utrasonography and CT. Recurrence rates of the remnant liver were significantly low and survival rates were significantly superior in the angio CT group compared to the other two groups (p<0.02). The prognosis with and without intermittent hepatic arterial infusion chemotherapy after hepatic resection were significantly different (p<0.03). The above data suggest that improvement of detection ratios for liver metastases by angio CT, and probably concomitant intermittent hepatic infusion chemotherapy contribute to decreased remnant liver recurrence and an increased survival rate.

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To determine the mode of recurrence of colorectal cancer, carcinoembryonic antigen doubling time (CEA-DT) was studied in 25 patients with recurrence after hepatectomy for heterochronous hepatic metastasis. Five patients (20.0%) had hepatic metastasis alone, 14 (56.0%) had hepatic metastasis besides other organ metastasis and 6 (24.0%) had other organ metastasis alone. After hepatectomy, in 13 patients (52.0%), the CEA-DTs were shorter, in 6 (24.0%), there was no change, and in 6 (24.0%), they were longer. The CEA-DTs were equal in the 5 patients whose site of recurrence was remnant liver alone. In the 20 patients whose recurrence sites were extrahepatic organs, the CEA-DTs after hepatectomy differed variably from those before hepatectomy (r=0.23, p=0.33). These findings suggest that the growth rate of hepatic metastatic tumors from colorectal cancer was constant even in remnant liver metastasis after hepatectomy. In the case of CEA-DT changing after hepatectomy, we suspect that there is metastasis to an extrahepatic organ, such as lung, peritoneum or local recurrence.

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It has been reported that gallbladder bile CEA levels could represent a sensitive index for the detection of occult hepatic metastases in patients with colorectal cancer. However, the mechanism of elevation of gallbladder bile CEA levels or the result of a follow-up study has not been fully clarified. In this study, the clinical value of gallbladder bile CEA measurement in patients with colorectal cancer was evaluated in regard to these problems. Gallbladder bile CEA levels in patients with liver metastasis were significantly higher than those in aptients without it (1182.9±1624.7vs 34.8± 69.9ng/ml, p<0.05). As a result of our follow-up study, the incidence of liver metastasis in patients with elevated gallbladder bile CEA levels more than 60ng/ml was found to be significantly higher than those in patients with gallbladder bile CEA levels less than 60ng/ml (42.9% vs 8%, p<0.05). There was a close correlation between the gallbladder bile CEA level and the grade of CEA stain in a metastatic liver lesion. In conclusion, we confirm that patients with elevation of gallbladder bile CEA levels (>60ng/ml) may be candidates for occult hepatic metastases, and suspect that elevation of gallbladder bile CEA levels in patients with liver metastasis is mainly due to direct secretion into the bile of CEA produced by the metastatic liver lesion.

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A total of 202 patients (139 males and 63 females) with early invasive colorectal cancer underwent resection in our department between 1970 and 1995. The mean age of the patients was 60.0±12.0 years and the average tumor diameter was 20.3±13.9 mm. The incidence of Ip (pedunculated) Isp (subpedunculated) and Is (sessile) type configuration was 140 cases (69.3%) and that of Ha (flat elevated) and IIa+ IIc (flat elevated with depression type) was 62 cases (30.7%). Early invasive colorectal cancer was located in the sigmoid colon and rectum in 80.7% of the patients. The 10 patients with lymph-node metastasis represented 4.9% of all early invasive cancer patients and the lymphovascular invasion, level of invasion, location and configuration were risk factors for development of lymph-node metastasis. Is (sessile) type and Ha+ IIc (flat elevated with depression) type early colorectal cancer had a high rate of lymph-node metastasis, and bowel resection must be performed as the treatment of first choice. All of the lymph-node metastases were paracolic lymph-node metastasis, and dissection of intermediate lymph nodes was thought to be enough for a curative operation of early invasive colorectal cancer.

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To ascertain the risk factors of metastasis, 102 patients with colorectal cancer invasing the muscularis propria were examined in terms of growth appearance and degree of invasion with an image analyzer. Type 1 tumors were larger in diamter in the mucosa and in overall tumor area than type 2 tumors. The deeper the invasion, the larger were the diameter and area of the tumor in the muscularis propria, but there was no relationship between the degree of invasion and either the tumor diameter or area in the mucosa. Thus no relationship was recognized between tumor diameter and degree of invasion in patients with colorectal cancer invading the muscularis propria. Although the presence or absence of metastasis to lymph node had no relation to the growth appearance and tumor area in the muscularis propria, the tumor area in the muscularis propria was usually small in patients with hematogenous metastasis (p=0.018) and the ratio of the tumor area in the muscularis propria to the overall tumor area was lower (p<0.01) than in patients without hematogenous metastasis. The frequency of hematogenous metastasis decreased with increasing degree of invasion, but the difference was not significant. These results suggest that it is difficult to predict metastasis from either the growth appearance or the degree of invasion in patients with colorectal cancer invading the muscularis propria. Rather, it is worth noting that the frequency of hematogenous metastasis is higher in patients with mild degree of invasion.

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Two cases of multifocal gastric carcinoid with and without type A gastritis are reported. A 49-year-old man was admitted for further evaluation of the stomach after endoscopic polypectomy of a carcinoid tumor. Marked hypergastrinemia (2200pg/ml) was observed. Total gastrectomy was performed and the resected specimen showed no obvious elevated lesion. But microscopically, pronounced atropy of the fundic glands (Type A gastritis) and multiple foci of carcinoids in the deeper layer of the propria mucosa to the submucosa were observed. The serum gastrin level returned to normal after the opearation. A 56-year-old man was admitted for treatment of an elevated lesion in the gastric body which was diagnosed as carcinoid. Wedge resection was performed and the specimen showed a main carcinoid lesion and a microcarcinoid. Total gastrectomy was performed 21 months after the first operation. Microscopically, multifocal carcinoid was observed but atrophy of the fundic gland was mild. These findings suggested that multifocal gastric carcinoid developed from type A gastritis or an other type gastritis.

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A 77-year-old man was admitted to our clinic with a complaint of discomfort in the upper abdomen. An upper gastrointestinal scopy revealed depressed lesion with an irregular border on the anterior side of the antrum. Histopathological examination showed a well-differentiated adenocarcinoma from the antral lesion. Preoperative blood chemical examination domonstrated a high level of serum CA19-9. Subtotal gastrectomy with DI lymphadenectomy was performed. Distant metastasis was not demonstrated. Microscopically, the resected stomach was found to have three depressed lesions. The largest lesion on the lesser curvature of the antrum invaded the submucosa and the others were limited to the mucosa. By immunohistochemical staining with anti-CA19-9 monoclonal antibody, partial expression of CA19-9 was detected. After the operation, the high level of serum CA19-9 was markably decreased to the normal serum level.

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The authors report the resected case of a adenosquamous carcinoma of the duodenum. In a 77-year-old man referred for investigation of anemia, upper gastrointestinal endoscopy revealed a tumor in the second portion of the duodenum. The endscopic biopsies showed adenocarcinoma and squamous cell carcinoma. Imaging studies and the operative findings disclosed that the tumor had invaded the head of the pancreas, portal vein and the transverse colon. Pancreaticoduodenectomy combined with right hemicolectomy was performed. The specimen revealed adenosquamous carcinoma of the duodenum. The patient has been well without any evidence of recurrence for 5 years after the surgery. A review of the literature and discussion about the histogenesis is included.

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Solitary tuberculoma of the liver is rare. A case of solitary tuberculoma of the liver after hepatectomy is described here. A 49-year-old man was admitted to our hospital, complaining of general fatigue and fever. He had a hepatectomy for a cholangiocarcinoma seven months earlier. Abdominal ultrasonography showed a low echoic, lesion 5 cm in diameter, in the remnant liver. Fine needle aspiration biopsy revealed no malignant finding, and Ziehl-Neelsen stain and culture for acid-fast bacilli were negative. Enhanced CT demonstrated a low-density lesion in the right anterior inferior (S5) and posterior inferior (S6) segment of the liver. Under the diagnosis of recurrent cholangiocarcinoma, partial resection of the liver was performed. The resected specimen showed a firm solid mass measuring 65×60×58mm. Histological findings revealed a caseous necrotic focus surrounded by the layers of epitheloid cells and fibrosis, which was compatible with tuberculoma. Ziehl-Neelsen stain and periodic acid-Schiff reaction were negative for bacilli and fungi. Histologically, this hepatic tumor was diagnosed as a solitary tuberculoma, although the tubercle bacillus was not in evidence.

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We have treated three cases of alimentary tract duplication in the last four years. Case 1 involved a 34-year-old man who had complained of abdominal pain since early childhood. On X-ray examination, an intra-abdominal calcification was detected. Although a definite diagnosis was not made, a laparotomy was performed because of the history of frequent severe abdominal pain. This led to diagnosis of duplication of the ileum. In case 2 a 13-year-old boy complained of abdominal pain and melena. Laparotomy was performed under a suspected diagnosis of Meckel's diverticulitis. A diagnosis of duplication of the ileum was then made. Case 3 involved a 67-year-old man who had undergone total gastrectomy because of gastric cancer. The operative findings included a tumor the size of a child's head was attached to the S-colon. We resected the tumor and made a diagnosis of duplication of the S-colon. The preoperative diagnosis of alimentary tract duplication is difficult. This potential diagnosis should be borne in mind for a patient who complains of abdominal symptoms with an unknown cause.

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A case of gastrointestinal bleeding from jejunal varices with extrahepatic port al obstruction was successfully treated by embolization of the varices by a transmesenteric approach under laparotomy. A 67-year-old man who had undergone pancreatoduodenectomy five months earlier for lower bile duct cancer was admitted to our hospital with massive gastrointestinal bleeding and he patic coma. The hepatic coma was treated by continuous arteriovenous hemofiltration; however, massive gastrointestinal bleedingoccurred again five months later. Angiography and color Doppler ultrasonography revealed the presence of extrahepatic portal obstruction and two streaks of hepatopetal collateral vessels which formed jejunal varices around the hepaticojejunostomy. Embolization of jejunal varices by a radiologic interventional technique was performed twice through the mesenteric vein following intraoperative portography.Bleeding has not recurred during the two years after the procedure. Embolization of varices is one of the useful therapeutic tools for gastrointestinal bleeding from ectopic varices.

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We report the case of an 86-year-old woman who received thermochemotherapy for advanced pancreatic cancer. She was given total parenteral nutrition (TPN) without vitamins because of decreaed food intake. Clouding of consciousness, peripheral circulatory failure, tachypnea and abdominal pain occurred suddenly 21 days after the start of TPN. Arterial blood gas analysis revealed severe metabolic acidosis (pH 7.193, base excess-6.6 mEq/l), which was refractory to the administration of sodium bicarbonate. After the administration of 150mg of thiamine intravenously, the level of consciousness and the severe acidosis were improved. The levels of serum lactate and blood vitamin B₁ at the onset were 119 mg/dl (normal range: 4-16) and 13 ng/ml (normal range: 25-50), respectively, and improved rapidly after thiamine therapy.

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Hemophilia A is a very rare disease and surgeon have the little patient with surgical disease. Since 1970, factor VIII concentrates was made available, hemostatic control has been straight forward easy and major surgery may be performed safely. In 1993, recombinant factor VIII was developed, but no case report of major surgery under supplementation of recombinant factor VIII have been published. We performed a successful total gastrectomy in a hemophilia A patient with gastric cancer under supplementation with recombinant factor VIII. Transfusion of recombinant factor VIII allowed good hemostatic control during and after the operation. This method of transfusion may be very useful because there is no fear of infection with unknown viruses or known viruses such as hepatitis virus and human immunodeficiency virus (HIV), and no possible effect from allo-antigen stimulator on the immune system.

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We performed transarterial infusion therapy (TAI) for 12 metastatic liver tumor patients with implantation of the catheter by the axillary arterial approach. Two radiologists implanted the catheter from the left axillary artery by Seldinger's method directly, without sheath-introducer, into the proper hepatic artery. In succession, the surgeon implanted the reservoir into the subcutaneous pocket on the lateral border of the left major pectoral muscle. The patient was allowed free walking just after the operation with resting of the left arm for 1 day. There were no serious complications. The duration of the operation was 118.8 minutes including the time for hemostasis at the punctured artery, and the period of hospitalization was 10.3 days including the time for preoperative examination and postoperative infusion therapy. Eleven patients were evaluable for the direct effect on the metastatic liver tumor, and one showed CR, 4 showed PR, 3 showed NC and 3 showed PD, with a responce rate of 45%. The mean survival was 775.4 days for H₁+H₂ cases and 626.2 days for H₃ cases. This method is thought to be useful for implantation of the catheter for TAI because of low invasiveness for the patients, short hospital stay for therapy and the necessity of only a few hands for the operation.

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We experienced a case of low-grade malignant insulinoma which was diagnosed by examining blood samples from the hepatic vein after selective intra-arterial calcium injections (SICI). A 77-year-old man who had had a history of epilepsy was treated by antiepileptic drugs for over 10 years. He was admitted to our hospital in an emergency because of unconsciousness. The blood glucose level was extremely low (29 mg/dl) and then the abdominal contrast-enhanced computed tomography showed a mass with a diameter of 1 cm in the body of the pancreas. Endoscopic retrograde cholangiography showed partial stenosis of the pancreatic ductin the body, which seemed to be caused by the extensive mass and dilatation of the pancreatic duct in the tail. However, the massive lesion was not detected by angiography. The serum insulin level in the hepatic vein by SICI into the distal splenic artery was over two times the control level. Therefore, this mass could be diagnosed as insulinoma in the tail of the pancreas. The body and tail of the pancreas were resected along with simultaneous splenectomy. The pathological diagnosis was made as islet cell carcinoma of low-grade malignancy and medullary type.

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We experimented with a vena cava filter for colon cancer compicated by pulmonary thromboembolism. The patient was a 78-year-old woman. When she was admitted to our hospital with pulmonary thromboembolism, anemia was pointed out and colon cancer was diagnsoed. In perioperatie management we gave her an anticoagulant and thrombolytic therapy and implanted a vena cava filter to prevent recurrence. Right colectomy was performed 37 days after admission. There has been no sign of recurrence of pulmonary thromboembolism or colon cancer, as of 2 years after surgery. In perioperative management for such a patient, the most important problem is to prevent recurrent pulmonary thromboembolism, but there have been no papers dealing with its perioperative management. Therefore, based on this case, we discussed thisproblem. Anticoagulant therapy plus the vena cava filter was effective. Especially we considered that the vena cava filter was beneficial for preventing recurrent pulmonary thromboembolism.

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There are three different types of clinically important bacteria, obligate anaerobes, facultative anaerobes, and obligate aerobes. Intestinal contents maintain anaerobic condition, and the intestinal bacterial flora is dominated by anaerobes. Intestinal bacteria suppressabnormal propagation with a synergic effect among species, produce immunoglobulin A, induce macrophage activity, and so on. Thus they play a part in defense against infection. However, postoperative infections, opportunistic infections, or bacterial translocations can be caused by intestinal bacteria. The intestinal flora, thus has merits and demerits for the human body. On the other hand there are many variant factors influencing intestinal flora. Treatment with histaminergic H2 receptor antagonists, gastric resection, antibiotic, total parenteral nutrition, etc. is important for a surgical patient. It is important to fully consider the weakness if antibiotic therapy, because postoperative prophylactic antibiotic therapy is inevitable in digestive tract surgery.

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The risk of postoperative infection is high in gastroenterological surgery, because bacterial contamination by the resident intestinal flora occurs easily and patients often suffer malnutrition.So it is important but very difficult to predict postoperative infection and take measures to deal with it.In this paper, I summarize the bacterial organisms, local environments, and host defense mechanisms in postoperative infections and discuss the preoperative evaluation and treatment of compromised hosts and the influence of surgical stress on postoperative infections.Moreover, I summarize the methods for early detection of postoperative infections and the frequency of causative organisms according to various types of postoperative infections or to various conditions of the patients to select the proper antibiotics for Dostoperative infections.Since prediction of postoperative infections is difficult, it is important to recognize the risk factors underlying these infections and to make an early diagnosis of the infection.

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The clinical significance of anaerobic infections continues to gain more ground as more ofthese bacteria are isolated in more and more medical facilities. Not only do they have a high detection rate, but also their toxicity levels should not be ignored. In patients in whom anaerobes had been detected, a great majority were mixed infections where a host of other bacterial agents came into play, although the anaerobes were often the majority in such cases. Anaerobes that are believed to be only mildly virulent may at times become highlypathogenic. For instance, even among anaerobic gram-negative rods, Bacteroides spp. and their production ofβ-lactamase, the enzyme enabling these bacteria to resist many third generation cephem drugs, are worth noting. Within the digestive tract, anaerobic bacteria are the majority among a spectrum of other bacteria; therefore, the prevention and treatment of infections including anaerobic infections becomes a necessity in the gastroenterological field.

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Appropriate antimicrobial therapy together with aseptic surgical procedures and necessary surgical drainage is an important element in controlling infections seen in gastroenterological surgery. For the treatment of primary surgical infections such as cholecystitis and peritonitis, empiric chemotherapy is performed by slecting the most appropriate antimicrobial agent through four steps. In those steps, factors including pathogens implicated in the infection, the pathogen's antimicrobial susceptibility, prevalence of resistant organisms, the agent's pharmacokinetics, the patient's host-defense status, and cost of the treatment are considered. With respect to prophylactic antimicrobial therapy for patients undergoing gastroenterological surgery, an antimicrobial agent is chosen and the length of the antimicrobial coverage is decided by considering the organ's normal flora, and the balance between the degree of contamination and the patient's host-defense status. The prophylactic therapy must be commenced immediately prior to the surgery and continued for not more than three postoperative days. For the treatment of postoperative infections, prompt empiricchemotherapy is crucial together with surgical drainage if necessary. To eradicate methicillin-resistant Staphylococcus aureus, vancomycin is a first-choice agent. However, abuse of vancomycin must be avoided to prevent development of a resistant stain.

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