79-YEAR OLD GENTLEMAN WITH PROGRESSIVE DYSPHAGIA ………………………………………………………………………………………………………………………………………………………………………………………………………………………………. FAISAL GHANI SIDDIQUI MBBS; FCPS (GENERAL SURGERY); PG DIPLOMA-BIOMEDICAL ETHICS; MCPS-HPE; FICLS; (MHPE) HEAD, SURGICAL UNIT-I PROFESSOR OF SURGERY CHAIRMAN, DEPARTMENT OF SURGERY & DIRECTOR, DEPARTMENT OF MEDICAL EDUCATION LIAQUAT UNIVERSITY OF MEDICAL & HEALTH SCIENCES faisalghani@lumhs.edu.pk

WHAT IS THE MOST LIKELY DIAGNOSIS? CASE REPORT A 79-year-old retired teacher was admitted in the surgery ward with H/O: Increasing difficulty in swallowing Initially could swallow soft diet but now can tolerate fluids only Weight loss of 5 kg in last one month On examination, he appears cachectic WHAT IS THE MOST LIKELY DIAGNOSIS?

DIAGNOSIS CARCINOMA ESOPHAGUS

WHAT IS THE THE DIFFERENTIAL DIAGNOSIS?

STAGES OF SWALLOWING 1: ORAL PHASE Voluntary; Under cortical control Food bolus is formed in the oral cavity and propelled backwards into the oropharynx by the movements of the tongue and soft palate 2: PHARYNGEAL PHASE Involuntary; Under brainstem control Food bolus is moved from the oropharynx to esophagus 3: ESOPHAGEAL PHASE Involuntary

DYSPHAGIA -difficulty in the progression of bolus from the mouth to the stomach due to dysfunction of: oropharynx esophagus Dysphagia is a symptom that refers to difficulty in the progression of the bolus from the mouth to the stomach. Dysphagia may result from oropharyngeal or esophageal dysfunction.

DIFFERENTIAL DIAGNOSIS OF DYSPHAGIA OROPHARYNGEAL DYSPHAGIA ESOPHAGEAL DYSPHAGIA DISEASES OF CNS CVA PARKINSON’S DISEASES ALZHEIMER'S DISEASE MULTIPLE SCLEROSIS DISEASES OF PERIPHERAL NERVOUS SYSTEM MYASTHENIA GRAVIS OBSTRUCTIVE LESIONS IN OROPHARYNX ZENKER’S DIVERTICULUM ENT TUMOURS ESOPHAGEAL MOTILITY DISORDERS ACHALASIA CARDIA DIFFUSE ESOPHAGEAL SPASM NUTCRACKER ESOPHAGUS EXTRINSIC COMPRESSION LYMPHADENOPATHY RETROSTERNAL GOITRE OBSTRUCTIVE LESIONS PEPTIC / CORROSIVE STRICTURES FOREIGN BODY CARCINOMA ESOPHAGUS If there is an abnormality in the muscles, nerves or structures of the oral cavity, pharynx, and upper esophageal sphincter, dysphagia is called oropharyngeal dysphagia. Oropharyngeal dysphagia may result from diseases of CNS (CVA, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis), diseases of peripheral nervous system (Myasthenia Gravis) and structural defects like ENT tumors, neck osteophytes, and Zenker’s diverticulum.

CARCINOMA OF THE OESOPHAGUS PATHOLOGY

CARCINOMA ESOPHAGUS –INCREASE IN INCIDENCE Incidence of carcinoma of the esophagus has risen in developed countries due primarily to an increase in adenocarcinoma. In the Far East, squamous cell carcinoma is more common.

3 TIMES MORE COMMON IN MALES The male to female ratio is 3:1.

TYPES OF CARCINOMA ESOPHAGUS 25% CARCINOMA OF OESOPHAGUS ADENOCARCINOMA SQUAMOUS CELL CARCINOMA 75 % One-third of carcinomas are of the lower one-third (adenocarcinoma, possibly from Barrett’s dysplasia) and two-thirds are of the upper two-thirds (predominantly squamous) of the esophagus.

SPREAD OF CARCINOMA OESOPHAGUS DIRECT INVASION BLOOD LYMPHATICS ACROSS THE WALL LONGITUDINALLY THROUGH SUBMUCOSAL LYMPHATICS TO THE REGIONAL LYMPH NODES Tumours can spread in three ways: invasion directly through the oesophageal wall, via the lymphatics or in the bloodstream. Direct spread occurs through the layers of the oesophageal wall as well as as longitudinally within the oesophageal wall. Longitudinal spread is mainly via the sub-mucosal lymphatic channels of the oesophagus. The pattern of lymphatic drainage is therefore not segmental, as in other parts of the GI tract. Consequently, the length of oesophagus involved by tumour is frequently much longer than the macroscopic length of the malignancy at the epithelial surface. Lymph node spread occurs commonly. Although the direction of spread to regional lymphatics is predominantly caudal, the involvement of lymph nodes is potentially widespread and can also occur in a cranial direction. Any regional lymph node from the superior mediastinum to the coeliac axis and lesser curve of the stomach may be involved, regardless of the location of the primary lesion within the oesophagus. Haematogenous spread may involve a variety of different organs including the liver, lungs, brain and bones. Tumours arising from the intra-abdominal portion of the oesophagus may also disseminate trans-peritoneally. LIVER LUNGS BONE

Carcinoma Esophagus disseminates early! Symptoms are often absent until tumour becomes advanced poor prognosis at the time of diagnosis! Both adenocarcinomas and squamous cell carcinomas tend to disseminate early. Sadly, the classic presenting symptoms of dysphagia, regurgitation and weight loss are often absent until the primary tumour has become advanced, and so the tumour is often well established before the diagnosis is made. Hence carries a poor prognosis with a 5-10 % 5-year survival rate.

WHY ME? RISK FACTORS

SQUAMOUS CELL CARCINOMA RISK FACTORS SQUAMOUS CELL CARCINOMA ADENOCARCINOMA SMOKING ALCOHOL HOT BEVERAGES CORROSIVE INJURY ACHALASIA CARDIA The most important risk factors for ADENOCARCINOMA are reflux and obesity, with a slightly increased risk of cardiac tumours with smoking. Risk factors for SQUAMOUS CELL CARCINOMA include alcohol, smoking, leucoplakia, achalasia, hot beverages, chewing tobacco and betel nuts, and corrosive injury of the esophagus. Tylosis palmarum is a rare autosomal recessive disorder, which is associated with a very high incidence of squamous cell carcinoma of the oesophagus. OBESITY --> REFLUX SMOKING

HOW WILL YOU INVESTIGATE THIS PATIENT? CASE REPORT A 79-year-old man admitted in the surgery ward with H/O: Increasing difficulty in swallowing Initially required soft diet but now can tolerate fluids Weight loss of 5 kg in last one month On examination, he appears cachectic HOW WILL YOU INVESTIGATE THIS PATIENT?

HOW TO INVESTIGATE PATIENT WITH DYSPHAGIA? 1 ENDOSCOPY BLOOD TESTS FOR FITNESS INVESTIGATIONS FOR STAGING 3 2 The diagnosis may be made initially by barium swallow, but must always be confirmed by endoscopy and biopsy. Endoscopy is the best first-line investigation for anyone with dysphagia.

ENDOSCOPY First-line investigation Site/size/extent/ histology of lesion Disadvantage: only mucosal surfaces biopsied Endoscopy is the first-line investigation for most patients. It provides an unrivalled direct view of the oesophageal mucosa and any lesion allowing its site and size to be documented. Cytology and/or histology specimens taken via the endoscope are crucial for accurate diagnosis. The combination of histology and cytology increases the diagnostic accuracy to more than 95%.

SQUAMOUS CELL CARCINOMA OF THE MID ESOPHAGUS NORMAL MUCOSA OF THE ESOPHAGUS SQUAMOUS CELL CARCINOMA OF THE MID ESOPHAGUS

HISTOPATHOLOGY SHOWS SQUAMOUS CELL CARCINOMA WHAT NEXT?

HOW TO INVESTIGATE PATIENT WITH DYSPHAGIA? 1 ENDOSCOPY INVESTIGATIONS FOR FITNESS INVESTIGATIONS FOR STAGING Local tumour and regional nodes (T, N) Endoscopic ultrasound Metastases (M) CT / PET scan (lung; liver; bones; distant nodes) Laparoscopy (peritoneal metastases) 3 2 Routine blood tests may reveal anaemia and malnutrition, all of which require full assessment if surgery is to be considered. Thereafter, investigations are aimed at accurate staging of the disease to assess resectability, determine prognosis and identify patients who might benefit from neoadjuvant therapy. Local T (tumour) stage and N (nodal) spread are best assessed by endoscopic ultrasonography. M (metastases) stage by CT and PET (lung, liver and bone metastases, distant lymphadenopathy), and laparoscopy (peritoneal metastases). If enlarged distant lymph nodes are detected, these should be aspirated for cytology, as surgical resection is contraindicated if they are positive for malignancy. Anemia Tests for malnutrition

MANAGING A PATIENT WITH SUSPICIOUS SYMPTOMS ENDOSCOPY & BIOPSY DIAGNOSIS OF CARCINOMA MADE ASSESS PATIENT’S FITNESS FOR SURGERY FIT STAGING INVESTIGATIONS UNFIT PALLIATION Endoscopy is the first-line investigation for most patients. It provides an unrivalled direct view of the oesophageal mucosa and any lesion allowing its site and size to be documented. Cytology and/or histology specimens taken via the endoscope are crucial for accurate diagnosis. The combination of histology and cytology increases the diagnostic accuracy to more than 95%. Once the initial diagnosis of a malignant oesophageal neoplasm has been made, patients should be assessed first in terms of their general health and fitness for potential therapies. Their preferences should also be considered. Most potentially curative therapies include radical surgery, although definitive chemoradiotherapy is an alternative in squamous cell carcinoma. Patients who are unfit for, or who do not wish to contemplate, radical treatments should not be investigated further, but should be diverted to appropriate palliative therapies, depending on the symptoms and current quality of life. Only those patients suitable for potentially curative therapies should proceed to staging investigations to rule out hematogenous spread (CT scan) and then to assess locoregional stage (endoscopic ultrasonography [EUS] ± laparoscopy). This will distinguish between early (T1/T2, N0) and advanced lesions (T3/T4, N1) and indicate whether surgery alone or multimodal therapy is most appropriate. Where attempted cure is deemed possible, the aim should be to provide the best chance of cure while minimizing procedural risks. In general, surgery alone should be reserved for patients with early dis- ease, and multimodal therapy should be used in patients with locally advanced disease, in whom the chance of cure by surgery alone is small (generally <20%). ADVANCED CURATIVE TREATMENT

LOCALLY ADVANCED DISEASE EARLY DISEASE T1/T2, N0 LOCALLY ADVANCED DISEASE T3/T4, N1 INCURABLE DISEASE Any T, N2/N3, M0 WHO TNM CLASSIFICATION

TREATMENT SURGERY RADICAL EARLY DISEASE SURGERY LOCALLY ADVANCED T1/T2, N0 LOCALLY ADVANCED DISEASE T2/T3, NO INCURABLE DISEASE Any T, N2/N3, M0 RADICAL SURGERY NEOADJUVANT CHEMOTHERAPY + SURGERY PALLIATION

TREATMENT SURGERY RADICAL EARLY DISEASE SURGERY LOCALLY ADVANCED T1/T2, N0 LOCALLY ADVANCED DISEASE T2/T3, NO INCURABLE DISEASE Any T, N2/N3, M0 RADICAL SURGERY NEOADJUVANT CHEMOTHERAPY + SURGERY PALLIATION

IVOR-LEWIS TWO PHASE ESOPHAGECTOMY Ivor–Lewis two-phase esophagectomy involves a laparotomy followed by a right thoracotomy.

IVOR-LEWIS TWO PHASE ESOPHAGECTOMY Ivor–Lewis two-phase esophagectomy involves a laparotomy during which the stomach is fully mobilised on its vascular pedicles, along with the lower esophagus. A right thoracotomy is carried out to resect the esophagus, and the mobilised stomach is brought up into the chest and anastomosed to the proximal esophagus. This is the preferred choice for middle and lower-third tumours.

MCKEOWN THREE PHASE ESOPHAGECTOMY McKeown three-phase esophagectomy involves a laparotomy to mobilise the stomach and lower esophagus, a right thoracotomy for mobilization of the thoracic esophagus and to perform a lymphadenectomy, and a left cervical incision to anastomose the stomach to the cervical esophagus. The advantages are avoidance of an anastomosis in the chest with its potential complications, and the ability to tackle mid- and upper-esophageal malignancies due to the high proximal clearance achieved along with adequate lymphadenectomy.

TREATMENT SURGERY RADICAL EARLY DISEASE SURGERY LOCALLY ADVANCED T1/T2, N0 LOCALLY ADVANCED DISEASE T2/T3, NO INCURABLE DISEASE Any T, N2/N3, M0 RADICAL SURGERY NEOADJUVANT CHEMOTHERAPY + SURGERY PALLIATION

SELF-EXPANDING METAL STENT Surgical resection and external beam radiotherapy may be used for palliation, but are not suitable when the expected survival is short, because most of the remainder of life will be spent recovering from the ‘treatment’. Surgical bypass is likewise too major a procedure for use in a patient with limited life expectancy. A variety of relatively simple methods of palliation is now available that will produce worthwhile relief of dysphagia with minimal disturbance to the patient. ENDOSCOPIC STENTING Patients with significant dysphagia should be considered for a palliative stent as this is a safe and effective method of relieving the distress of not being able to swallow. These are inserted under intravenous sedation endoscopically but can also be screened into position by interventional radiologists. ENDOSCOPIC LASER Treatment may be used to core a channel through the tumour. BRACHYTHERAPY A method of delivering intraluminal radiation with a short penetration distance (hence the pre- fix ‘brachy’) to a tumour.

CASE REPORT A 79-year-old man admitted in the surgery ward with H/O: Increasing difficulty in swallowing Initially required soft diet but now can tolerate fluids Weight loss of 5 kg in last one month On examination, he appears cachectic CONCLUSION: This case report demonstrated the importance of a timely upper endoscopy. It carries major impact on primary care physicians who serve as the first tier in managing patients with ‘red flag’ features.

. . . IN SUMMARY Squamous cell affects the upper two-thirds; adenocarcinoma affects the lower third Common etiological factors are tobacco and alcohol (squamous cell), GORD and obesity (adenocarcinoma) Dysphagia is the most common presenting symptom Accurate pretreatment staging is essential in patients thought to be fit to undergo ‘curative’ treatment